Is CASK p.Val412= (c.1236A>G) pathogenic?

CASK p.Val412= (c.1236A>G) is classified Likely benign in CASK (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-06-17). Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with CASK p.Val412= (c.1236A>G)?

CASK p.Val412= (c.1236A>G) is associated with Inborn genetic diseases (ClinVar).

How common is CASK p.Val412= (c.1236A>G) in the general population?

CASK p.Val412= (c.1236A>G) is absent from gnomAD v4.1 (gnomAD).

CASK p.Val412=

c.1236A>G · rs2519845032 · VCV1756848

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,092,726)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.5	GERP 0.083, phastCons 1
Overall
CADD	11.4	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,092,726). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CASK
Protein: p.Val412=
Coding: c.1236A>G
MANE Select: NM_001367721
dbSNP: rs2519845032
Type: single nucleotide variant
Location: chrX:41586985 (GRCh38)
Structure: AlphaFold pLDDT 79.45 · 22 PDB
Residue 412: a UniProt-annotated variant site (found in a patient with epilepsy and pontocerebellar hypoplasia; likely pathogenic); the l27 2 domain; an α-helix

Full CASK gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CASK p.Ala300Thr Uncertain significance ★★ ⚠ same condition
CASK p.Arg560Trp Uncertain significance ★★ ⚠ same condition
CASK p.Arg766Trp Uncertain significance ★★ ⚠ same condition
CASK p.Asn31Ser Uncertain significance ★★ ⚠ same condition
CASK p.Asp330Gly Uncertain significance ★★ ⚠ same condition
CASK p.Asp498Gly Uncertain significance ★★ ⚠ same condition
CASK p.Glu662Asp Uncertain significance ★★ ⚠ same condition
CASK p.Gly21Asp Uncertain significance ★★ ⚠ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/cask-p-val412 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown